Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke

Hesse, Camilla; Rosengren, Lars; Andreasen, Niels; Davidsson, Pia; Vanderstichele, Hugo; Vanmechelen, Eugeen; Blennow, Kaj

doi:10.1016/s0304-3940(00)01697-9

Cited by 399 publications

(293 citation statements)

References 19 publications

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“…16 In addition, the higher CSF levels of P-tau compared to total tau found in this and other studies 12,17,18 may be caused by the application of different standards. A synthetic peptide was used in P-tau and a recombinant protein for the total tau ELISA.…”

Section: Discussionmentioning

confidence: 64%

“…The MMSE was used to test cognitive ability in control subjects. In each patient structural MRI imaging and in subjects with AD and FTD additional functional imaging using 18 FDG PET was performed. Visual rating of functional images helped to classify patients with FTD as every patient with FTD had markedly frontal or anterior temporal hypometabolism.…”

Section: Methodsmentioning

confidence: 99%

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Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt–Jakob disease from other dementias

et al. 2003

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Early clinical symptoms of sporadic Creutzfeldt-Jakob disease (CJD) may overlap with other neurodegenerative diseases like Alzheimer's disease (AD) and frontotemporal degeneration (FTD). On entering an era in which pharmaceutical treatment of CJD occurs, reliable diagnostic markers like immunodetection of 14-3-3 proteins in the cerebrospinal fluid (CSF) are required. However, false negative results in autopsy-proven, sporadic CJD cases, as well as false positive results in several other disorders including AD and FTD showing high CSF tau protein levels, limit the potential of this marker. Due to neuronal lysis the cytosolic fraction of total tau containing phosphorylated and non-phosphorylated isoforms is partially liberated into the CSF. Since hyperphosphorylation of tau may specifically occur in neurodegenerative diseases associated with neurofibrillary changes, we hypothesized that the phospho-tau (P-tau)/total tau ratio in CSF may be a useful marker to discriminate CJD from other neurodegenerative disorders. The P-tau/total tau ratio discriminated patients with CJD from all other neurodegenerative disorders including patients with AD and FTD without any overlap. Although the results have to be confirmed in a larger sample, the preliminary data suggest that simultaneous measurement of total tau and P-tau in CSF may be useful to identify patients with CJD.

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Section: Discussionmentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt–Jakob disease from other dementias

et al. 2003

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“…In the AN1792 trial reduced levels of T-tau were seen in AD patients immunized against Ab and interpreted as a possible reduction of cellular degeneration (Gilman et al 2005). Patients with stroke initially have increased T-tau levels, which normalize after a few months (Hesse et al 2001). In amateur boxers, head trauma leads to increased T-tau levels, which normalize after a few months of rest (Zetterberg et al 2006).…”

Section: Amyloid Markersmentioning

confidence: 99%

Miglustat Treatment May Reduce Cerebrospinal Fluid Levels of the Axonal Degeneration Marker Tau in Niemann–Pick Type C

et al. 2011

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Introduction: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder that leads to progressive neurodegeneration. The glucosylceramide synthase blocker miglustat is being used to treat NPC, but monitoring of disease progression and treatment response is difficult. NPC patients have elevated cerebrospinal fluid (CSF) levels of total-tau (T-tau) indicating axonal degeneration, and increased CSF amyloid b (Ab) indicating abnormal brain amyloid metabolism, but it is unknown if start of miglustat treatment affects these biomarker levels.Methods: Biomarkers were measured in serial CSF samples from NPC patients who started miglustat between samplings (N ¼ 5), were untreated at both samplings (N ¼ 5) or received treatment during the whole study (N ¼ 6) (median time between samplings 309 days [range 175-644]). CSF was analyzed for Ab 38 , Ab 40 , Ab 42 , a-cleaved soluble APP, b-cleaved soluble APP, T-tau and phospho-tau.Results: T-tau levels decreased in patients who started miglustat treatment (median 955 [range 338-1,271] ng/L at baseline vs. 382 ng/L at follow-up, p ¼ 0.043). Untreated patients and continuously treated patients had stable levels (p > 0.05). No changes were seen in the other biomarkers.Conclusion: Reduced CSF T-tau suggests that miglustat treatment might affect axonal degeneration in NPC. However, the results must be interpreted with caution and verified in future studies, since this pilot study was small, treatment was not randomized, and patients starting treatment had higher baseline CSF T-tau than untreated patients.

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“…This hypothesis comes from indirect evidence such as the finding that there is no change in CSF P-tau after acute stroke, 25 although there is a marked increase in T-tau. 18 Furthermore, CSF P-tau lev-els are normal or only mildly increased in CJD despite a very marked increase in T-tau.…”

Section: Tau Proteinmentioning

confidence: 99%

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

2004

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Summary:The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has made patients seek medical advice at an earlier stage of the disease. This has highlighted the importance of diagnostic markers for early AD. However, there is no clinical method to determine which of the patients with mild cognitive impairment (MCI) will progress to AD with dementia, and which have a benign form of MCI without progression. In this paper, the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is reviewed. The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of ␤-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson's disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia. Early diagnosis of AD is not only of importance to be able to initiate symptomatic treatment with AChE inhibitors, but will be the basis for initiation of treatment with drugs aimed at slowing down or arresting the degenerative process, such as ␥-secretase inhibitors, if these prove to affect AD pathology and to have a clinical effect.

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Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke

Cited by 399 publications

References 19 publications

Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt–Jakob disease from other dementias

Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt–Jakob disease from other dementias

Miglustat Treatment May Reduce Cerebrospinal Fluid Levels of the Axonal Degeneration Marker Tau in Niemann–Pick Type C

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

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